This application's long-term objectives are investigation of neuroendocrine changes responsible for age-related loss of reproductive cycles. The specific aims of this application are to use the technique of high performance liquid chromatography to determine age-related changes in the activities of enzymes involved in the synthesis and degradation of catecholamines and serotonin in discrete areas of the hypothalamus. Age-related changes in the contents and release of catecholamines and serotonin and gonadotropin releasing hormone from discrete areas of the hypothalamus will also be determined. The technique of push-pull perfusion will be used to determine the release of neurotransmitters and gonadotropin releasing hormone from hypothalamic areas. The data on the activities of the enzymes and on the content and release of neurotransmitters will be collected on a long-term basis during various patterns of acyclicity and correlated with serum levels of luteinizing hormone, prolactin, estradiol and progesterone and with vaginal cytology. Changes in these parameters will also be determined after acyclic animals have been treated with -dopa and after normal cyclic animals have been on chronic treatment with estradiol. The data collected in this project will explain in detail the age- related changes in the activities of the enzymes involved in the synthesis and degradation of catecholamines and serotonin and in the hypothalamic content and release of these neurotransmitters. These data will be new and will add to our understanding of the primary causes of loss of reproductive cyclicity in aging.